Increased interregional virus exchange and nucleotide diversity outline the expansion of chikungunya virus in Brazil.

The emergence and reemergence of mosquito-borne diseases in Brazil such as yellow fever, zika, chikungunya, and dengue have had serious impacts on public health. Concerns have been raised due to the rapid dissemination of the chikungunya virus across the country since its first detection in 2014 in Northeast Brazil. In this work, we carried out on-site training activities in genomic surveillance in partnership with the National Network of Public Health Laboratories that have led to the generation of 422 chikungunya virus genomes from 12 Brazilian states over the past two years (2021-2022), a period that has seen more than 312 thousand chikungunya fever cases reported in the country. These genomes increased the amount of available data and allowed a more comprehensive characterization of the dispersal dynamics of the chikungunya virus East-Central-South-African lineage in Brazil. Tree branching patterns revealed the emergence and expansion of two distinct subclades. Phylogeographic analysis indicated that the northeast region has been the leading hub of virus spread towards other regions. Increased frequency of C > T transitions among the new genomes suggested that host restriction factors from the immune system such as ADAR and AID/APOBEC deaminases might be driving the genetic diversity of the chikungunya virus in Brazil.

Phylogenetic Reconstructions Reveal the Circulation of a Novel Dengue Virus-1V Clade and the Persistence of a Dengue Virus-2 III Genotype in Northeast Brazil.

Dengue fever is among the most significant public health concerns in Brazil. To date, the highest number of Dengue notifications in the Americas has been reported in Brazil, with cases accounting for a total number of 3,418,796 reported cases as of mid-December 2022. Furthermore, the northeastern region of Brazil registered the second-highest incidence of Dengue fever in 2022. Due to the alarming epidemiological scenario, in this study, we used a combination of portable whole-genome sequencing, phylodynamic, and epidemiological analyses to reveal a novel DENV-1 genotype V clade and the persistence of DENV-2 genotype III in the region. We further report the presence of non-synonymous mutations associated with non-structural domains, especially the NS2A (non-structural protein 2A), as well as describe synonymous mutations in envelope and membrane proteins, distributed differently between clades. However, the absence of clinical data at the time of collection and notification, as well as the impossibility of monitoring patients in order to observe worsening or death, restricts our possibility of correlating mutational findings with possible clinical prognoses. Together, these results reinforce the crucial role of genomic surveillance to follow the evolution of circulating DENV strains and understand their spread across the region through inter-regional importation events, likely mediated by human mobility, and also the possible impacts on public health and outbreak management.

Increased interregional virus exchange and nucleotide diversity outline the expansion of the chikungunya virus ECSA lineage in Brazil.

The emergence and reemergence of mosquito-borne diseases in Brazil such as Yellow Fever, Zika, Chikungunya, and Dengue have had serious impacts on public health. Concerns have been raised due to the rapid dissemination of the chikungunya virus (CHIKV) across the country since its first detection in 2014 in Northeast Brazil. Faced with this scenario, on-site training activities in genomic surveillance carried out in partnership with the National Network of Public Health Laboratories have led to the generation of 422 CHIKV genomes from 12 Brazilian states over the past two years (2021-2022), a period that has seen more than 312 thousand chikungunya fever cases reported in the country. These new genomes increased the amount of available data and allowed a more comprehensive characterization of the dispersion dynamics of the CHIKV East-Central-South-African (ECSA) lineage in Brazil. Tree branching patterns revealed the emergence and expansion of two distinct subclades. Phylogeographic analysis indicated that the northeast region has been the leading hub of virus spread towards other regions. Increased frequency of C>T transitions among the new genomes suggested that host restriction factors from the immune system such as ADAR and AID/APOBEC deaminases might be driving CHIKV ECSA lineage genetic diversity in Brazil.

COVID-19 outbreaks among crew members in non-cruise vessels anchoring in Salvador, Brazil, 2021.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected the maritime sector due to virus transmission onboard and traffic restrictions. However, reports of SARS-CoV-2 transmission on board have been mostly restricted to those occurring on cruise ships. OBJECTIVES: To report COVID-19 outbreaks in eight non-cruise vessels and discuss measures to prevent and control the onboard transmission of SARS-CoV-2. METHODS: We investigated outbreaks of COVID-19 on vessels anchoring in Baía de Todos-os-Santos, Salvador, Brazil, between February and November 2021. FINDINGS: Most vessels were cargo ships that had docked several times before anchoring in Salvador (five had docked in ≥ 9 ports). The crew ranged from 22 to 63 members. The infection attack rate on each vessel ranged from 9.7 to 88.9%. The risk of symptomatic infection largely varied among the crew of each vessel (0 to 91.6%). Overall, the risk of developing COVID-19 signs and symptoms was lower among crew members vaccinated (age-adjusted risk ratio: 0.19; 95% confidence interval 0.06-0.65). SARS-CoV-2 variants not previously identified in Salvador were detected (C.14, B.1.617.2 and B.1.351). MAIN CONCLUSIONS: Despite maritime guidelines to avert COVID-19 on board, outbreaks have happened. The multiple stopovers of non-cruise vessels during their routes may contribute to the spread of SARS-CoV-2 variants worldwide. Reducing the onboard transmission of SARS-CoV-2 depends on joint efforts by the crew and local health authorities and, equally important, achieving high vaccination coverage to prevent infections and illness.

Low prevalence of influenza A strains with resistance markers in Brazil during 2017-2019 seasons.

The influenza A virus (IAV) is of a major public health concern as it causes annual epidemics and has the potential to cause pandemics. At present, the neuraminidase inhibitors (NAIs) are the most widely used anti-influenza drugs, but, more recently, the drug baloxavir marboxil (BXM), a polymerase inhibitor, has also been licensed in some countries. Mutations in the viral genes that encode the antiviral targets can lead to treatment resistance. Worldwide, a low prevalence of antiviral resistant strains has been reported. Despite that, this situation can change rapidly, and resistant strain surveillance is a priority. Thus, the aim of this was to evaluate Brazilian IAVs antiviral resistance from 2017 to 2019 through the identification of viral mutations associated with reduced inhibition of the drugs and by testing the susceptibility of IAV isolates to oseltamivir (OST), the most widely used NAI drug in the country. Initially, we analyzed 282 influenza A(H1N1)pdm09 and 455 A(H3N2) genetic sequences available on GISAID. The amino acid substitution (AAS) NA:S247N was detected in one A(H1N1)pdm09 strain. We also identified NA:I222V (n = 6) and NA:N329K (n = 1) in A(H3N2) strains. In addition, we performed a molecular screening for NA:H275Y in 437 A(H1N1)pdm09 samples, by pyrosequencing, which revealed a single virus harboring this mutation. Furthermore, the determination of OST IC50 values for 222 A(H1N1)pdm09 and 83 A(H3N2) isolates revealed that all isolates presented a normal susceptibility profile to the drug. Interestingly, we detected one A(H3N2) virus presenting with PA:E119D AAS. Moreover, the majority of the IAV sequences had the M2:S31N adamantanes resistant marker. In conclusion, we show a low prevalence of Brazilian IAV strains with NAI resistance markers, in accordance with what is reported worldwide, indicating that NAIs still remain an option for the treatment of influenza infections in Brazil. However, surveillance of influenza resistance should be strengthened in the country for improving the representativeness of investigated viruses and the robustness of the analysis.

Retrospective Investigation in Horses with Encephalitis Reveals Unnoticed Circulation of West Nile Virus in Brazil.

During these past years, several studies have provided serological evidence regarding the circulation of West Nile virus (WNV) in Brazil. Despite some reports, much is still unknown regarding the genomic diversity and transmission dynamics of this virus in the country. Recently, genomic monitoring activities in horses revealed the circulation of WNV in several Brazilian regions. These findings on the paucity of genomic data reinforce the need for prompt investigation of WNV infection in horses, which may precede human cases of encephalitis in Brazil. Thus, in this study, we retrospectively screened 54 suspicious WNV samples collected between 2017 and 2020 from the spinal cord and brain of horses with encephalitis and generated three new WNV genomes from the Ceará and Bahia states, located in the northeastern region of Brazil. The Bayesian reconstruction revealed that at least two independent introduction events occurred in Brazil. The first introduction event appears to be likely related to the North American outbreak, and was estimated to have occurred in March 2013.The second introduction event appears to have occurred in September 2017 and appears to be likely related to the South American outbreak. Together, our results reinforce the importance of increasing the priority of WNV genomic monitoring in equines with encephalitis in order to track the dispersion of this emerging pathogen through the country.

Dynamics and Determinants of SARS-CoV-2 RT-PCR Testing on Symptomatic Individuals Attending Healthcare Centers during 2020 in Bahia, Brazil.

RT-PCR testing data provides opportunities to explore regional and individual determinants of test positivity and surveillance infrastructure. Using Generalized Additive Models, we explored 222,515 tests of a random sample of individuals with COVID-19 compatible symptoms in the Brazilian state of Bahia during 2020. We found that age and male gender were the most significant determinants of test positivity. There was evidence of an unequal impact among socio-demographic strata, with higher positivity among those living in areas with low education levels during the first epidemic wave, followed by those living in areas with higher education levels in the second wave. Our estimated probability of testing positive after symptom onset corroborates previous reports that the probability decreases with time, more than halving by about two weeks and converging to zero by three weeks. Test positivity rates generally followed state-level reported cases, and while a single laboratory performed ~90% of tests covering ~99% of the state's area, test turn-around time generally remained below four days. This testing effort is a testimony to the Bahian surveillance capacity during public health emergencies, as previously witnessed during the recent Zika and Yellow Fever outbreaks.

Unusual SARS-CoV-2 intrahost diversity reveals lineage superinfection.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected almost 200 million people worldwide by July 2021 and the pandemic has been characterized by infection waves of viral lineages showing distinct fitness profiles. The simultaneous infection of a single individual by two distinct SARS-CoV-2 lineages may impact COVID-19 disease progression and provides a window of opportunity for viral recombination and the emergence of new lineages with differential phenotype. Several hundred SARS-CoV-2 lineages are currently well phylogenetically defined, but two main factors have precluded major coinfection/codetection and recombination analysis thus far: (i) the low diversity of SARS-CoV-2 lineages during the first year of the pandemic, which limited the identification of lineage defining mutations necessary to distinguish coinfecting/recombining viral lineages; and the (ii) limited availability of raw sequencing data where abundance and distribution of intrasample/intrahost variability can be accessed. Here, we assembled a large sequencing dataset from Brazilian samples covering a period of 18 May 2020 to 30 April 2021 and probed it for unexpected patterns of high intrasample/intrahost variability. This approach enabled us to detect nine cases of SARS-CoV-2 coinfection with well characterized lineage-defining mutations, representing 0.61 % of all samples investigated. In addition, we matched these SARS-CoV-2 coinfections with spatio-temporal epidemiological data confirming its plausibility with the cocirculating lineages at the timeframe investigated. Our data suggests that coinfection with distinct SARS-CoV-2 lineages is a rare phenomenon, although it is certainly a lower bound estimate considering the difficulty to detect coinfections with very similar SARS-CoV-2 lineages and the low number of samples sequenced from the total number of infections.

COVID-19 outbreaks among crew members in non-cruise vessels anchoring in Salvador, Brazil, 2021

BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected the maritime sector due to virus transmission onboard and traffic restrictions. However, reports of SARS-CoV-2 transmission on board have been mostly restricted to those occurring on cruise ships. OBJECTIVES To report COVID-19 outbreaks in eight non-cruise vessels and discuss measures to prevent and control the onboard transmission of SARS-CoV-2. METHODS We investigated outbreaks of COVID-19 on vessels anchoring in Baía de Todos-os-Santos, Salvador, Brazil, between February and November 2021. FINDINGS Most vessels were cargo ships that had docked several times before anchoring in Salvador (five had docked in ≥ 9 ports). The crew ranged from 22 to 63 members. The infection attack rate on each vessel ranged from 9.7 to 88.9%. The risk of symptomatic infection largely varied among the crew of each vessel (0 to 91.6%). Overall, the risk of developing COVID-19 signs and symptoms was lower among crew members vaccinated (age-adjusted risk ratio: 0.19; 95% confidence interval 0.06-0.65). SARS-CoV-2 variants not previously identified in Salvador were detected (C.14, B.1.617.2 and B.1.351). MAIN CONCLUSIONS Despite maritime guidelines to avert COVID-19 on board, outbreaks have happened. The multiple stopovers of non-cruise vessels during their routes may contribute to the spread of SARS-CoV-2 variants worldwide. Reducing the onboard transmission of SARS-CoV-2 depends on joint efforts by the crew and local health authorities and, equally important, achieving high vaccination coverage to prevent infections and illness.

The ongoing evolution of variants of concern and interest of SARS-CoV-2 in Brazil revealed by convergent indels in the amino (N)-terminal domain of the spike protein.

Mutations at both the receptor-binding domain (RBD) and the amino (N)-terminal domain (NTD) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike (S) glycoprotein can alter its antigenicity and promote immune escape. We identified that SARS-CoV-2 lineages circulating in Brazil with mutations of concern in the RBD independently acquired convergent deletions and insertions in the NTD of the S protein, which altered the NTD antigenic-supersite and other predicted epitopes at this region. Importantly, we detected the community transmission of different P.1 lineages bearing NTD indels ∆69-70 (which can impact several SARS-CoV-2 diagnostic protocols), ∆144 and ins214ANRN, and a new VOI N.10 derived from the B.1.1.33 lineage carrying three NTD deletions (∆141-144, ∆211, and ∆256-258). These findings support that the ongoing widespread transmission of SARS-CoV-2 in Brazil generates new viral lineages that might be more resistant to antibody neutralization than parental variants of concern.

Seroprevalence and Spatial Distribution of Hepatitis C Virus in Bahia, Brazil.

In Salvador, which is the capital of the Brazilian state of Bahia, it has been estimated that 1.5% of the general population is infected with hepatitis C virus (HCV); however, the circulation of HCV throughout the state remains unknown. The present retrospective study aimed to determine anti-HCV seroprevalence and describe the geographic distribution of hepatitis C in Bahia. Data from HCV serological tests submitted to the Bahia Central Laboratory of Public Health between 2004 and 2013 were analyzed. Serology for HCV was performed using the AxSYM anti-HCV enzymatic microparticle immunoassay and chemiluminescence immunoassay. A subgroup of samples with detectable HCV-RNA was genotyped using the linear array hepatitis C virus genotyping assay. A total of 247,837 samples were analyzed. The median age of the studied population was 31 years (interquartile range, 25-44 years), and the female:male ratio was 3.9:1. The global seroprevalence of HCV in Bahia was estimated to be 1.3% (3,230/247,837), corresponding to an infection rate of 21.2/100,000 inhabitants. The seroprevalence of HCV was higher among males and increased with age. The presence of anti-HCV antibodies was detected throughout all mesoregions of Bahia, and the municipality with the highest infection rate was Ipiaú (112.04 cases/100,000 inhabitants). Genotypes 1 and 3 were found to be the most prevalent, followed by genotypes 2, 4, and 5. Our results provide evidence of the widespread distribution of previous HCV infection throughout the state of Bahia.

Field and classroom initiatives for portable sequence-based monitoring of dengue virus in Brazil.

Brazil experienced a large dengue virus (DENV) epidemic in 2019, highlighting a continuous struggle with effective control and public health preparedness. Using Oxford Nanopore sequencing, we led field and classroom initiatives for the monitoring of DENV in Brazil, generating 227 novel genome sequences of DENV1-2 from 85 municipalities (2015-2019). This equated to an over 50% increase in the number of DENV genomes from Brazil available in public databases. Using both phylogenetic and epidemiological models we retrospectively reconstructed the recent transmission history of DENV1-2. Phylogenetic analysis revealed complex patterns of transmission, with both lineage co-circulation and replacement. We identified two lineages within the DENV2 BR-4 clade, for which we estimated the effective reproduction number and pattern of seasonality. Overall, the surveillance outputs and training initiative described here serve as a proof-of-concept for the utility of real-time portable sequencing for research and local capacity building in the genomic surveillance of emerging viruses.

Evaluation of the Inflammatory Cytokines and IL-10 Network in Individuals Co-infected With Human T-Cell Lymphotropic Virus and Hepatitis C Virus (HTLV/HCV).

BACKGROUND: Co-infection between the human T-cell lymphotropic virus (HTLV) and the hepatitis C virus (HCV) can modify the natural history of HCV infection. The aim of this study was to describe the inflammatory cytokines and IL-10 network in patients co-infected with HTLV and HCV viruses in Bahia, Brazil. METHODS: Samples from 31 HTLV/HCV co-infected individuals and 27 HCV monoinfected individuals were evaluated. IFN-γ, TNF-α, IL-10, IL-8, and IL-1 cytokines were quantified by ELISA. Clinical, laboratory data were obtained from patient records. Serum levels of the cytokines were log10-transformed and data mining was performed using Z-score statistics and correlation analysis. RESULTS: Co-infected individuals presented a tendency toward higher production of INF-γ compared to the HCV monoinfected group. Regarding cytokine pairs, there was a positive correlation (P-value < 0.05) between IL-1 and IL-8 in the HTLV/HCV co-infected group and uninfected controls, and two correlations in the HCV mono-infected group IL-8 - IL10 and IL- INF-γ - IL-10 pairs. There was no significant difference between the groups for the other parameters analyzed. CONCLUSION: The results presented herein indicated that HTLV/HCV co-infection was associated with a trend in IFN-γ production while HCV-infected individuals presented a positive correlation with both inflammatory cytokines (IL-8 and IFN-γ) and the regulatory cytokine IL-10.

Experiência do laboratório central de Saúde Pública da Bahia no enfrentamento da pandemia da Covid-19 / Experience of the central laboratory of Public Health of Bahia in coping with the Covid-19 pandemic / Experiencia del laboratorio central de Salud Pública de Bahía en el afrontamiento de la pandemia Covid-19

A Covid-19 é uma doença infecciosa causada pelo novo coronavírus, denominado SARS-CoV-2, que causou um surto de pneumonia viral incomum em pacientes em Wuhan, na China, no final do ano de 2019. O vírus se disseminou pelo mundo em grandes proporções, atingindo o status epidemiológico de pandemia. Diante desse cenário, que afetou toda a Federação brasileira, o Laboratório Central de Saúde Pública Professor Gonçalo Moniz (Lacen-BA) tem exercido papel fundamental no diagnóstico da Covid-19 e na vigilância genômica do SARS-CoV-2. Nesse sentido, este estudo tem como objetivo descrever as estratégias implementadas pelo Lacen-BA para ampliar a capacidade diagnóstica e atender a demanda da rede SUS-BA no contexto da pandemia da Covid-19. Trata-se de um estudo descritivo-observacional, orientado por um modelo lógico sustentado em quatro dimensões: parque tecnológico, metodologias analíticas, descentralização do exame e monitoramento de indicadores de resultados. As iniciativas de gestão possibilitaram ampliação da capacidade instalada e operacional, mediante modernização da estrutura física, renovação do parque tecnológico, reorganização dos fluxos e processos de trabalho, aporte de novas tecnologias analíticas e estruturação de dashboard para monitorar indicadores e subsidiar o processo decisório. O Lacen-BA, enquanto coordenador da Rede Estadual de Laboratórios de Saúde Pública e sistema de apoio da Rede de Atenção à Saúde (RAS), constitui-se então em estruturas policêntricas essenciais para o diagnóstico descentralizado e regionalizado da Covid-19, contribuindo para a integração sistêmica das ações e serviços no contexto da regionalização da saúde, de modo a garantir a universalidade do acesso e integralidade dos cuidados aos usuários do SUS.

Covid-19 is an infectious disease caused by the new coronavirus, called SARS-CoV-2, which caused an outbreak of unusual viral pneumonia in patients in Wuhan, China, at the end of 2019 and spread across the world, in large proportions, reaching the epidemiological status of a pandemic. Considering this epidemiological scenario that affected the entire Brazilian Federation, the Central Laboratory of Public Health Professor Gonçalo Moniz (Lacen-BA) has played a fundamental role in the diagnosis of Covid-19 and the genomic surveillance of SARS-CoV-2. In this sense, this study aims at describing the strategies implemented by Lacen-BA to expand the diagnostic capacity to meet the demand of the SUS-BA network, in the context of the Covid-19 pandemic. This is a descriptive-observational study, guided by a logical model based on four dimensions: technological park, analytical methodologies, decentralization of the exam and monitoring of result indicators. The management initiatives enabled the expansion of the installed and operational capacity by modernizing the physical structure, renewing the technological park, reorganizing workflows and processes, providing new analytical technologies, structuring the dashboard to monitor indicators and support the decision-making process. The Lacen-BA, as coordinator of the State Public Health Laboratory Network and support system of the Health Care Network (RAS), constitutes essential polycentric structures for the decentralized and regionalized diagnosis of Covid-19, which can contribute to the systemic integration of actions and services in the context of regionalization of health to guarantee the universality of access and comprehensive care to SUS users.

El covid-19 es una enfermedad infecciosa causada por el nuevo coronavirus, llamado SARS-CoV-2, que provocó un brote de neumonía viral inusual en pacientes en Wuhan, China, a fines de 2019, y que se extendió por el mundo, en grandes proporciones hasta alcanzar el estado epidemiológico de pandemia. Ante este escenario epidemiológico que afectó a Brasil, el Laboratorio Central de Salud Pública Profesor Gonçalo Moniz (Lacen-BA) ha jugado un papel fundamental en el diagnóstico del covid-19 y la vigilancia genómica del SARS-CoV-2. En este sentido, este estudio tiene como objetivo describir las estrategias implementadas por Lacen-BA para ampliar la capacidad de diagnóstico y atender la demanda de la red SUS-BA, en el contexto de la pandemia del Covid-19. Este estudio es descriptivo-observacional, guiado por un modelo lógico con base en cuatro dimensiones: parque tecnológico, metodologías analíticas, descentralización del examen y seguimiento de indicadores de resultado. Las iniciativas de gestión permitieron ampliar la capacidad instalada y operativa al modernizar la estructura física, renovar el parque tecnológico, reorganizar los flujos y procesos de trabajo, brindar nuevas tecnologías analíticas y estructuración del cuadro de mando para monitorear indicadores, y apoyar la toma de decisiones. Lacen-BA, como coordinador de la Red Estadual de Laboratorios de Salud Pública y sistema de apoyo de la Red de Atención a la Salud (RAS), constituye estructuras policéntricas imprescindibles para el diagnóstico descentralizado y regionalizado del Covid-19, que pueden contribuir a la integración sistémica de acciones y servicios en el contexto de la regionalización de la salud, a fin de garantizar la universalidad del acceso y la atención integral a los usuarios del SUS.

Distribution of Human Immunodeficiency Virus and Human T-Leukemia Virus Co-infection in Bahia, Brazil.

Human Immunodeficiency Virus (HIV) and Human T-Leukemia Virus (HTLV) are retroviruses that share similar routes of transmission. In Brazil, the prevalence of HIV and HTLV varies according to geographic region. The state of Bahia, located in the Northeast region, is considered endemic for both retroviruses. The present study aimed to characterize the frequency of HIV/HTLV coinfection and evaluate the geographic distribution of coinfection throughout the state. This cross-sectional study was conducted at the state's Central Laboratory of Public Health (LACEN-BA) and included all samples from 2004 to 2013 submitted to serological testing for anti-HIV and anti-HTLV-1/2, screened by chemiluminescence/ELISA and confirmed by Western blot. Infection rates are expressed as the number of infected individuals per 100,000 inhabitants from each municipality. A total of 129,158 samples originating from 358/417 (85.8%) municipalities in Bahia were evaluated. HTLV was detected in 2.4% of the HIV-positive samples (n = 42) compared to 0.5% of those with negative HIV serology (n = 677) (OR: 4.65; CI: 3.39-6.37). HIV/HTLV coinfection was more frequent in women (69.0%); the median age of coinfected individuals was 47.2 years [interquartile range (IQR): 41.6-55.4 years]. In the 14/417 (3.4%) municipalities where at least one case of HIV/HTLV coinfection was detected, the overall HTLV coinfection rate in HIV-positive samples was 0.25 (range: 0.17-13.84) per 100,000 inhabitants. Most cases of HIV/HTLV-1 coinfection (21/37, 57%) were concentrated in the municipality of Salvador. Isolated instances (one or two cases) of HIV/HTLV-1 coinfection were distributed across municipalities known to be endemic for HTLV infection.

Unusual SARS-CoV-2 intra-host diversity reveals lineages superinfection

Em períodos como o da presente pandemia de SARS-CoV-2, em que diversas linhagens e variantes de um mesmo vírus circulam simultaneamente em uma população, a ocorrência de coinfecções é sempre uma preocupação. Definidas como eventos nos quais uma mesma pessoa ou célula encontra-se infectada por duas ou mais amostras virais de perfil genético distinto, as coinfecções podem representar um risco à saúde coletiva caso tornem possíveis eventos de recombinação, ou seja, novos perfis genéticos virais derivados de uma "mescla" entre as linhagens genéticas que infectam o mesmo paciente. O presente trabalho, desenvolvido por pesquisadores de diversas unidades da Fiocruz vinculados à Rede Genômica e publicado sob a forma de preprint (sem revisão independente por outros pesquisadores), investiga o fenômeno das reinfecções com base em 2.263 amostras de SARS-CoV-2, utilizando métodos de análise com uso de computadores desenvolvidos pela própria Fiocruz. Estes métodos permitiram identificar sinais de alta variabilidade nos dados de sequenciamento do genoma, variabilidade esta associada ao sequenciamento simultâneo de mais de um perfil genético viral.

Distribution of Human T-Lymphotropic Virus (HTLV) and Hepatitis C Co-infection in Bahia, Brazil.

Both Human T-lymphotropic virus type 1 (HTLV-1) and hepatitis C virus (HCV) are endemic in Brazil. In Salvador, the capital of the state of Bahia, 2% and 1.5% of the general population is infected with HTLV-1 or HCV. This study aimed to estimate the prevalence and the distribution of HTLV/HCV coinfection in Bahia. This cross-sectional study was conducted at the Central Laboratory of Public Health for the state of Bahia (LACEN-BA). All samples in the LACEN database submitted to serological testing for anti-HCV (chemiluminescence) and anti-HTLV-1/2 (chemiluminescence/ELISA and Western blot) from 2004 to 2013 were included. Infection rate was expressed as the number of infected individuals per 100,000 inhabitants in a given municipality; municipalities were grouped by microregion for further analysis. A total of 120,192 samples originating from 358 of the 417 municipalities in Bahia (85.8%) were evaluated. The overall HCV coinfection rate in HTLV-positive was 14.31% [2.8 (ranging from 0.4 to 8.0) per 100,000 inhabitants.] Twenty-one (5%) of the municipalities reported at least one case of HTLV/HCV coinfection. Most cases (87%) were concentrated in three microregions (Salvador: 79%, Ilhéus/Itabuna: 5%, Porto Seguro: 3%). Coinfection occurred more frequently in males (51%) with a mean age of 59 [(IQR): 46-59] years. HTLV/HCV coinfection in the state of Bahia was more frequently found among males living in the microregions of Salvador, Ilhéus/Itabuna and Porto Seguro, all of which are known to be endemic for HTLV infection.

Evidence of New Endemic Clusters of Human T-Cell Leukemia Virus (HTLV) Infection in Bahia, Brazil.

BACKGROUND: Salvador, Bahia (northeastern Brazil), has been identified as the epicenter of Human T-cell leukemia virus Human T-cell leukemia virus (HTLV) type 1 infection in the country. This study aims to estimate the rate of HTLV infection and the geographical distribution of this virus in this state. METHODS: All HTLV tests (chemiluminescence/ELISA assays/Western Blotting) performed in the Central Laboratory of Public Health of Bahia (LACEN) from 2004 to 2013 were included. Data was extracted from LACEN's database using high volume extract, transformation and load throughput. Infection rate was expressed as the number of infected individuals per 100,000 inhabitants considering municipalities grouped in microregions and/or mesoregions as the unit of analysis. RESULTS: A total of 233,876 individuals were evaluated. Individuals were from 394 out of 417 municipalities of Bahia (94.5%). HTLV chemiluminescence/ELISA assay was found to be reactive for 3,138 individuals from whom 2,323 had WB results (1,978 positives, 62 negative and 282 indeterminate). Out of 1978 reactive samples, 1,813 (91.7%) were positive for HTLV-1, 58 (2.9%) for HTLV-2 and 107 (5.4%) were for both HTLV-1 and HTLV-2. The cumulative mean rate of HTLV-positive cases in Bahia was 14.4 per 100,000 inhabitants. Three microregions presented rates >20 HTLV-positive cases/100,000 inhabitants: Barreiras (24.83 cases per 100,000 inhabitants), Salvador (22.90 cases per 100,000 inhabitants), and Ilhéus-Itabuna (22.60 cases per 100,000 inhabitants). CONCLUSION: HTLV infection is disseminated in the state of Bahia, with an overall moderate rate of infection. Further studies should be conducted to characterize the epidemiological and clinical profile of HTLV-infected individuals better and to propose effective prevention measures.

Taxa de infecção do vírus linfotrópico de células T humanas (HTLV), vírus da hepatite C (HCV), coinfecção HTLV/HCV no estado da Bahia e impacto da coinfecção HTLV/HCV no perfil de citocinas / Infection rate of Human T-cell lymphotropic virus (HTLV), hepatitis C virus (HCV), HTLV / HCV coinfection in state of the Bahia and impact of HTLV / HCV coinfection on cytokine profile

Iintrodução: Os vírus linfotrópico de células T humanas (HTLV) e vírus da hepatite C (HCV) são endêmicos no Brasil. Ambos causam uma infecção persistente, assintomática em alguns casos, sendo o diagnóstico tardio. Estes vírus compartilham algumas vias de transmissão, o que pode favorecer a coinfecção. OBJETIVOS: Determinar a taxa de infecção do HTLV, HCV e coinfecção HTLV/HCV no estado da Bahia. Descrever o perfil de citocinas inflamatórias nos indivíduos coinfectados com HTLV/HCV. Métodos: Um estudo retrospectivo ecológico foi conduzido usando o banco de dados do LACEN ­ Bahia. Todos os testes sorológicos para HTLV e HCV foram selecionados entre as 32 microrregiões da Bahia, no período de 2004 a 2013, constituindo um banco com 602.908 registros únicos. Para a avaliação imune, foram selecionados prospectivamente amostras de 31 indivíduos coinfectados HTLV/HCV e de 27 indivíduos monoinfectados com HCV, recebidas no LACEN para quantificar a carga viral do HCV no período de 2014 a 2016. Foram analisadas as citocinas IFN-γ, TNF-α, IL-10, IL-8 e IL-1. O grupo controle foi formado por 30 indivíduos sadios. Resultados: Foram avaliadas 233.876 amostras para o diagnóstico laboratorial do HTLV. Destas, 1.813 (91,7%) foram positivas para HTLV-1 (prevalência de 0,78%), 58 (2,9%) para HTLV-2 (prevalência de 0,025%) e 107 (5,4%) foram positivas para ambos HTLV-1 e HTLV-2 (prevalência de 0,05%). A taxa de infecção na Bahia foi 0,84% (14,4 casos /100.000 habitantes). A infecção pelo HTLV foi predominante em mulheres (75%) com média de idade de 46 anos. Foram identificados três novos clusters do HTLV, localizados nas regiões Sul, Central e Oeste do estado. Amostras de 247.837 indivíduos foram avaliadas para o diagnóstico laboratorial do HCV. A taxa de infecção do HCV foi de 1,3% que corresponde a 21,2 casos/ 100.000 habitantes. Os homens com idade acima de 55 anos foram os mais acometidos. A cidade de Ipiaú apresentou a maior taxa de infecção para o HCV (112,04 casos/100.000 habitantes). Os genótipos 1 e 3 foram mais prevalentes, seguidos dos genótipos 2, 4 e 5. Para determinar a taxa de coinfecção entre HTLV e HCV amostras de 120.192 indivíduos foram avaliados. A taxa de infecção do HTLV/HCV foi de 14,3% que equivale a 2,8 casos/100.000 habitantes. Os casos de coinfecção HTLV/HCV predominou em homens com média de idade de 59 anos. As maiores taxas foram encontradas em três microrregiões: Salvador, Ilhéus-Itabuna e Porto Seguro. Quanto ao perfil de citocinas, o grupo coinfectados HTLV/HCV teve uma maior tendência a produzir IFN-γ, comparado ao grupo monoinfectado HCV. Houve uma correlação positiva entre os pares IL-1 e IL-8 no grupo coinfectado pelo HTLV/HCV e entre os pares IL-8 - IL10 e INF-γ - IL-10 no grupo monoinfectado pelo HCV. Conclusões: As infecções pelo HTLV e HCV estão disseminadas nas microrregiões do estado Bahia, no entanto a coinfecção HTLV/HCV está concentrada em apenas três microrregiões. A coinfecção HTLV/HCV está associada à produção de IFN-γ, enquanto indivíduos infectados pelo HCV apresentaram correlação positiva entre as citocinas inflamatórias (IL-8 e IFN-γ) e a citocina reguladora IL-10